Gao Zhonggao, Kennedy Anne M, Christensen Douglas A, Rapoport Natalya Y
Department of Bioengineering, University of Utah, Salt Lake City, UT 84112, USA.
Ultrasonics. 2008 Aug;48(4):260-70. doi: 10.1016/j.ultras.2007.11.002. Epub 2007 Nov 19.
A new class of multifunctional nanoparticles that combine properties of polymeric drug carriers, ultrasound imaging contrast agents, and enhancers of ultrasound-mediated drug delivery has been developed. At room temperature, the developed systems comprise perfluorocarbon nanodroplets stabilized by the walls made of biodegradable block copolymers. Upon heating to physiological temperatures, the nanodroplets convert into nano/microbubbles. The phase state of the systems and bubble size may be controlled by the copolymer/perfluorocarbon volume ratio. Upon intravenous injections, a long-lasting, strong and selective ultrasound contrast is observed in the tumor volume indicating nanobubble extravasation through the defective tumor microvasculature, suggesting their coalescence into larger, highly echogenic microbubbles in the tumor tissue. Under the action of tumor-directed ultrasound, microbubbles cavitate and collapse resulting in a release of the encapsulated drug and dramatically enhanced intracellular drug uptake by the tumor cells. This effect is tumor-selective; no accumulation of echogenic microbubbles is observed in other organs. Effective chemotherapy of the MDA MB231 breast cancer tumors has been achieved using this technique.
已开发出一类新型多功能纳米颗粒，它兼具聚合物药物载体、超声成像造影剂以及超声介导药物递送增强剂的特性。在室温下，所开发的系统由可生物降解嵌段共聚物构成的壁所稳定的全氟碳纳米液滴组成。加热至生理温度时，纳米液滴会转变为纳米/微泡。系统的相态和气泡大小可通过共聚物/全氟碳体积比来控制。静脉注射后，在肿瘤体积中观察到持久、强烈且选择性的超声造影，这表明纳米气泡通过有缺陷的肿瘤微血管发生了外渗，意味着它们在肿瘤组织中聚合成更大、高回声的微泡。在肿瘤靶向超声的作用下，微泡空化并塌陷，导致封装药物释放，肿瘤细胞对细胞内药物的摄取显著增强。这种效应具有肿瘤选择性；在其他器官中未观察到回声微泡的积累。使用该技术已实现对MDA MB231乳腺癌肿瘤的有效化疗。
